AU Binding Proteins Recruit the Exosome to Degrade ARE-Containing mRNAs
Open accessAbstract
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3' untranslated regions. Although found 15 years ago, the mechanism by which AREs dictate rapid mRNA decay is not clear. In yeast, 3'-to-5' mRNA degradation is mediated by the exosome, a multisubunit particle. We have purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. Using a cell-free RNA decay system, we demonstrate that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. The mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition requires certain ARE binding proteins that can interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.
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The RNA exosome has specialized functions in RNA splicing and regulation of AU-rich element (ARE)-containing transcripts.
“In addition to RNA turnover, the RNA exosome has specialized functions in RNA splicing and the regulation of AU-rich element (ARE)-containing transcripts44–47.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [46]
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“The RNA exosome complex has also been shown to degrade RNA transcripts with specific regulatory elements 46 .”
- Authors
- Chen, C.-Y., Gherzi, R., Ong, S.-E., Chan, E. L., Raijmakers, R., Pruijn, G. J. M., Stoecklin, G., Moroni, C., Mann, M., & Karin, M.
- Affiliations
- University of California San Diego (US)
- University of Southern Denmark (DK)
- Radboud University Nijmegen (NL)
- University of Basel (CH)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 107
- Issue
- 4
- Pages
- 451-464
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2152432732
- Cited by
- 865
- References
- 1
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 18 · 2023: 10 · 2022: 17 · 2021: 17 · 2020: 26 · 2019: 27 · 2018: 16 · 2017: 17 · 2016: 26 · 2015: 33 · 2014: 32 · 2013: 37 · 2012: 38
- FWCI
- 18.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- AU-rich elements, exosomes, mRNA degradation, 3' untranslated region, exosome composition, mRNA stability
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell-Free System, Humans, Interleukin-2, Mammals, Molecular Sequence Data, Poly A, Recombinant Fusion Proteins, RNA, Messenger, RNA, Neoplasm, Thymine Nucleotides, Trans-Activators, Sequence Alignment, RNA-Binding Proteins, Genes, fos, Sequence Homology, Amino Acid, Jurkat Cells, Base Pairing, 3' Untranslated Regions, Gene Silencing
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